DLL4 Gene: Delta Like Canonical Notch Ligand 4
Key regulator of angiogenesis and Notch signaling pathway
Gene Information Card
| Symbol | DLL4 |
|---|---|
| Full Name | Delta Like Canonical Notch Ligand 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 54567 ncbi.nlm.nih.gov/gene/54567 |
| Ensembl ID | ENSG00000128917 |
| UniProt ID | Q9NR61 |
| OMIM ID | 605185 |
| HGNC ID | 2910 |
| Aliases | delta4, hdelta4, delta-like 4, delta-like protein 4 |
Description
DLL4 encodes a transmembrane ligand for Notch receptors, playing a critical role in the Notch signaling pathway. It is essential for vascular development, angiogenesis, and cell fate determination. DLL4 is predominantly expressed in endothelial cells and regulates tip cell formation during sprouting angiogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alagille syndrome | Heterozygous loss-of-function mutations in DLL4 disrupt Notch signaling, leading to developmental defects in bile ducts, heart, and vasculature. | OMIM #605185; PMID: 29304373 |
| Cerebral cavernous malformations | DLL4 mutations impair endothelial cell-cell junctions and vascular stability via Notch pathway dysregulation. | ClinVar; PMID: 29304373 |
| Cancer (multiple types) | DLL4 overexpression promotes tumor angiogenesis and growth; inhibition of DLL4 reduces tumor vascularization. | COSMIC; PMID: 17463249 |
| Adams-Oliver syndrome | Rare DLL4 variants associated with limb and scalp defects, linked to Notch signaling disruption. | OMIM #614219; PMID: 25758994 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.3 | Medium |
| Lung | 9.8 | Medium |
| Placenta | 15.6 | High |
| Kidney | 7.2 | Low |
| Liver | 4.1 | Low |
| Brain | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (endothelial) | 45.2 | High expression; key for angiogenesis studies |
| HeLa | 3.1 | Low expression |
| A549 | 2.8 | Low expression |
| MCF7 | 1.5 | Very low expression |
| K562 | 0.9 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1066C>T (p.Arg356*) | Nonsense | <0.01% | Loss of function; truncation of protein |
| c.1370G>A (p.Arg457Gln) | Missense | <0.01% | Impaired ligand-receptor binding |
| c.1660_1661del (p.Leu554fs) | Frameshift | <0.01% | Loss of function; protein truncation |
| c.1972G>A (p.Gly658Arg) | Missense | <0.01% | Reduced Notch signaling activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that reduce or abolish DLL4-Notch binding or signaling, associated with Alagille syndrome and Adams-Oliver syndrome.
Gain of Function (GOF)
Not well characterized; some missense variants may increase Notch signaling, but evidence is limited.
Dominant Negative (DN)
Truncated DLL4 proteins can interfere with wild-type DLL4 function, leading to haploinsufficiency in Alagille syndrome.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG: hsa04330)
• Angiogenesis (Reactome: R-HSA-194138)
• Signaling by Notch (Reactome: R-HSA-157118)
Protein Summary
DLL4 is a 685-amino acid transmembrane protein with a Delta/Serrate/Lag-2 (DSL) domain essential for Notch receptor activation. It is highly expressed in endothelial cells and regulates vascular sprouting, arterial specification, and tumor angiogenesis. Mutations in DLL4 cause developmental disorders such as Alagille syndrome and Adams-Oliver syndrome, while its overexpression is implicated in cancer progression.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLL4 Knockout HEK293 Cell Line | EDJ-KQ417 | Human | 54567 | Details Get a Quote |
| DLL4 Knockout HeLa Cell Line | EDJ-KQ56440 | Human | 54567 | Details Get a Quote |
| DLL4 Knockout A-549 Cell Line | EDJ-KQ64934 | Human | 54567 | Details Get a Quote |
| DLL4 Knockout HCT 116 Cell Line | EDJ-KQ73376 | Human | 54567 | Details Get a Quote |
